This invention relates generally to freeze drying devices and the lyophilization procedures they implement and particularly relates to unattended operation of a freeze drying device that maintains the integrity of the samples to be dried during implementation of a freeze drying procedure.
Known freeze drying devices, such as in U.S. Pat. 4,017,983, assigned to the owner of this application require trained and experienced operators properly to effect lyophilization of a sample or samples; often the operators are the researchers themselves. The operators must exercise care in effecting the lyophilization process to protect and maintain the integrity of the samples that have been collected over periods as long as a year.
Attaching a sample bottle to the manifold of a device not ready to receive samples can result in the frozen sample melting and splattering over the interior of the manifold chamber and fouling the vacuum pump. In such a case, at least, the device must be warmed to room temperature and the manifold opened for cleaning. This results in a loss of use of the device, the cost of having trained and experienced people clean the device and possibly replace the vacuum pump, not to mention the enormous loss, in time and money, of the samples collected through diligent and hard work over a long period.
Often the lyophilization process takes an extended period to effect and so the device is left operating unattended overnight or over a weekend. Normally the device operates satisfactorily as long as the electrical power to the device continues uninterrupted. In the event of a power failure, however, the device simply returns to its set mode of operation upon return of the electricity. If the outage occurred for a short period, the return should cause no problem because the samples remain frozen and within their sample bottles.
An outage lasting a long time, however, will allow the samples to melt. When the device returns to its set mode of operation, the reduced pressure in the device causes the samples to boil up into the device and into the vacuum pump. This can result in a worse problem and loss of time and money than when samples are applied to the device before it is ready to receive them. Even if the samples have become substantially dried by the time of the outage, turning on the vacuum pump before the necessary reduction of temperature in the device can ruin the pump by pulling melted condesate or ice water into the pump.
After completion of a lyophilization process or the collection of a maximum amount of ice, the condenser in the manifold of the device must be defrosted. The operator turns off the vacuum pump, immediately turns a valve to open the vacuum chamber to the atmosphere and sets the refrigeration system to run in reverse for heating the condenser. Normally the heating of the condenser melts the ice in a short period and the water drains from the chamber. Even here problems can occur. The chamber must be opened to the atmosphere soon after turning off the pump; otherwise the pump oil backs up into the chamber, which then must be cleaned. If the refrigeration system becomes turned off, the ice will still melt, but over an extended period instead of quickly. If the device runs in the defrost mode after the ice melts and unattended for an extended period, such as over the weekend, the compressor of the refrigeration system experiences unnecessary wear.
The prior solutions to these and associated problems have been to provide competent and responsible operators to stand at the freeze drying devices while they are passing through the described cycles. This becomes an expensive solution when the operators could be performing other valuable and productive duties instead of waiting for the freeze dryer to complete a cycle. Further, the prior devices have failed to furnish a simple and positive indication to an operator of the time at which sequential operations, such as turning on the vacuum pump after the condenser reaches a desired low temperature, could or should be performed. This requires that the operators be well trained to effect the sequencing of the device and to know the symptoms of an improper condition, such as a cracked sample bottle preventing the re-establishment of the vacuum. Constructing and arranging the freeze dryer devices to operate unattended would free the researchers for other more important and productive activities.